The long-term objective of my laboratory is to understand how genetic changes contribute to the survival, adaptation, and evolution of organisms. All organisms live in biotic and abiotic environments that change over time. Sensory genes are responsible for detecting these environmental changes and thus play a pivotal role in the daily life of organisms, including humans. Chemoreception is of particular interest because of the tremendous diversity of chemicals that organisms recognize and respond to. Here we focus on the evolution of vertebrate genes and genetic pathways responsible for two chemosensations that have significant evolutionary ramifications and mechanistic similarities: vomeronasal pheromone detection and tastant detection. These two systems enable vertebrates to find nutritious food and suitable mates, and to avoid predators and toxic substances. Two unrelated large superfamilies, V1 Rs and V2Rs, serve as pheromone receptors in vomeronasal sensory neurons, and the ion channel TRPC2 is indispensable in vomeronasal transduction. Bitter tastants are recognized in taste buds by a family of T2R receptors that are evolutionary related to V1 Rs, whereas sweet and umami tastants are detected by T1R receptors that are related to V2Rs. Micro- and macro-evolution of pheromone and taste receptions will be examined using genetic/genomic approaches. Our specific aims are (1) to test predictions of intra-specific variation and inter-specific divergence of V1R and V2R genes using two closely related mouse species;(2) to examine the macro- evolutionary patterns of vertebrate V1 Rs and V2Rs by genomic analysis, including tests of hypotheses on a shift of V1R/V2R repertoires in the emergence of land vertebrates, on coevolution of V1R/V2R genes with other genes, and on the losses of V2R genes in various vertebrates;(3) to study the origin of the vomeronasal system by tracing the system-specific genes in early diverging vertebrates and chordates;(4) to assess the functionality of V1R genes in humans and related apes that lack a functional vomeronasal organ by population genetic and evolutionary analyses;(5) to study the macro-evolution of vertebrate T1 Rs and T2Rs by comparative genomic analysis;and (6) to test the hypothesis of relaxation of functional constraints on human bitter taste receptors by population genetic analysis of T2Rs in humans and related apes. These studies will also help understand human smell and taste variations and disorders.